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Journal of Computational Mathematics 2008年第1期26卷 76-97页

作者： Igor Boglaev matthew hardy Institute of Fundamental Sciences Massey UniversityPrivate Bag 11-222Palmerston NorthNew Zealand Mathematical Sciences Institute Australian National UniversityCanberraAustralia 0200

This paper presents and analyzes a monotone domain decomposition algorithm for solving nonlinear singularly perturbed reaction-diffusion problems of parabolic type. To solve the nonlinear weighted average finite difference scheme for the partial differential equation, we construct a monotone domain decomposition algorithm based on a Schwarz alternating method and a box-domain decomposition. This algorithm needs only to solve linear discrete systems at each iterative step and converges monotonically to the exact solution of the nonlinear discrete problem. domain decomposition algorithm is estimated The rate of convergence of the monotone Numerical experiments are presented.

关键词： Parabolic reaction-diffusion problem Boundary layers O-method Monotone domain decomposition algorithm Uniform convergence

Arrested Proliferation of Progenitor and Immature Leydig Cells Accounting For the Reduced Leydig Cell Number in Igf-I Null Mice

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Arrested Proliferation of Progenitor and Immature Leydig Cel...

邻苯二甲酸酯类化合物与睾丸源性生殖障碍综合征

2006年浙江省病理学术会议暨第三届中国国际淋巴造血系...

作者： Chantal M Sottas matthew P hardy Center for Biomedical Research Population Council and Rockefeller UniversityNew YorkNYUnited States10021 Center for Biomedical Research Population Council and Rockefeller UniversityNew YorkNYUnited States10021

＜Abstract＞Aim Backgound: Normal numbers of adult Leydig cells per testis are is maintained primarily from the normal proliferation of its progenitors. Postnatal development of Leydig cells in rodents can be divided into four distinct stages of differentiation: initially fibroblast-like stem Leydig cells （SLC） proliferates by postnatal days （PND） 7 to 14, and then they commit to fibroblast-like progenitors （PLC） by 14-21;subsequently, as immature Leydig cells （ILC） by day 21-35, they acquire steroidogenic organelle structure and enzyme activities but metabolize most of the testosterone they produce;finally, as adult Leydig cells （ALC） by day 90 they actively produce testosterone. Targeted gene deletion of insulin-like growth factor-I （IGF-I） results in diminished numbers of Leydig cells （LCs） and lower circulating testosterone levels in adult males. Aim: The aims of the present study were to determine dynamic proliferating and differentiating profiles of adult Leydig cell population during postnatal period in IGF-I null mice. Methods: Testicular cells in mice were labeled by injection of BrDU and testes were collected by PND14, 21, 28, 56 and 90. Leydig cells were immunohistochemically stained using 3β-hydroxysteroid dehydrogenase antibody and analyzed using a imaging analytical software. Results: SLC become proliferative at PND 14 in wild-typed testis with labeling index of 10.8±4.6 （Mean±SEM）, LI of SLC greatly decreased through PND 21-56, and LI peaked for PLC at PND 21 and LI for LC peaked at PND 35. LI of SLC did not change in IGF-I null mice （7.4±3.3） compared to wild-type mice, while PLC and ILC did not proliferate through PND 14 to PND90. The Leydig cell number and cell size were significantly reduced in IGF-I mutant adult testis, e.g. at PND90, 980±155 cells/mm2 and 132.6±6.4μm2 compared to 1876±116 cells/mm2 and 280.9±10.6 μm2 in wild-type testis, respectively. The differentiation of SLC into PLC was not affected since the numbers of PLC formed at PND14 was

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中华男科学杂志 2007年第3期13卷 195-200页

作者：陈国荣董磊葛仁山 matthew P.hardy 浙江省温州医学院附属第一医院病理科 Population Council and Rockefeller University 1230 York AvenueNew YorkNew York10021USA

流行病学研究显示妇女在怀孕期间接触邻苯二甲酸酯类化合物后,所产男婴易患隐睾、尿道下裂、成年期睾丸肿瘤及精液质量低下等症状。这类症状可统称为睾丸源性生殖障碍综合征(testicular dysgenesis syndrome,TDS)。TDS可能是由男性胎儿... 详细信息

流行病学研究显示妇女在怀孕期间接触邻苯二甲酸酯类化合物后,所产男婴易患隐睾、尿道下裂、成年期睾丸肿瘤及精液质量低下等症状。这类症状可统称为睾丸源性生殖障碍综合征(testicular dysgenesis syndrome,TDS)。TDS可能是由男性胎儿睾丸的发育在子宫内受到影响不能发育出具有正常功能的睾丸间质(Leydig)细胞和支持(Sertoli)细胞引起的。例如,睾丸间质细胞接触邻苯二甲酸酯类化合物后,睾丸间质细胞的两种产物———睾酮和胰岛素样生长因子3(INSL3)———受到了抑制,两者对于睾丸下降起关键作用。成年期睾丸的胎儿型间质细胞和支持细胞错位可能是精子生成减少的原因。

关键词：邻苯二甲酸酯睾丸源性生殖障碍综合征流行病学怀孕男性胎儿

Nicotine Acetylcgoline Receptor Expression and Nicotineinduced modulation of Testosterone(T) producton in rat leydig cells

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Development of a cryopreservation protocol for leydig cells

2006年浙江省病理学术会议暨第三届中国国际淋巴造血系统疾病诊断及治疗新进展研讨会

作者： Chantal M.Sottas matthew P.hardy Population Council Now YorkNew York 10021 USA

It has been reported that neuronal signaling directly controls Leydig cell steroidogenic function. Neuronal pathways to the testis and to the vicinity of Leydig cells have been demonstrated, but neurotransmitter senstitivity in these cells has remained unclear. The objectives of the present study were to determine if acetylcholine receptors (AchRs) are expressed in Leydig cells. Progenitor, immature and adult Leydig cells were purified from 21-, 35-and 90-day-old male Sprague Dawley rats, respectively, and AchR messenger RNA levels were measured by DNA macro- arrays. The nicotinic-AchR subunits α1,α2,α3,α4,α5,α6,α7,β1,β2,Δ,γ,and σ,and muscarinic AchR M2 through M5 were all included in the analysis. Subunits α1,α5, α4, α6,β1, β2, and σ were detected above significant signal threshold levels. None of the muscarinic receptor forms were detected. Subunit α4 had the highest signal level: it was undetectable in progenitor Leydig cells and increased sharply during the transitions to immature and adult Leydig cell by up to 100 fold. Transcript levels for the enzyme acetylcholinseterase, which metabolizes Ach, were also abundant. Adult Leydig cells were cytotoxically eliminated from adult testes by administration of the drug ethylene dimethanesulfonate. This induced Leydig cell regeneration, and it was noted that a4 subunit expression was eliminated along with the Leydig cells and reappeared only after 35 days with the restoration of normal serum testosterone concentrations. Purified adult Leydig cells were treated with different concentrations of nicotine (10-7 to 10-3M) for 3 hours. Nicotine exerted a biphasic dose response for LH stimulated T production. Lower doses, 10-5M, increased T levels by 20% (control 141±5 vs.171±9ng/106cell·3hr), whereas higher doses,e.g., 10-3M,lowered T production by 50% (71±1ng/106cells·3hr). Therefore, at physiological concentrations of agonist, the AchR pathway is stimulatory. These data suggest that nicotinic AchR signaling may be

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Development of a cryopreservation protocol for leydig cells

11 β-HSD控制糖皮质激素对睾酮合成抑制的研究———11 β-HSD mRNA的表达

2006年浙江省病理学术会议暨第三届中国国际淋巴造血系统疾病诊断及治疗新进展研讨会

作者： Chatal M.Sottas matthew P.hardy Population Council New YorkNew York 10021USA

Lmplantation of Leydig cells either in suspension or encapsulated in alginatepoly-Llysine microspheres has been proposed as a possible treatment of hypogonadism. A protocol for effective cryopreservation of these cells pror to implantation has been developed. Progenitor(PLC), immature(lLc)and adult rat Leydig cells (ALC)were purified from 21-35-and 90-dayold rats by Percoll separation. The cells were re-suspended in a culture medium supplemented with 1% bovine serum albumin (S-DMEM/F12)in a final concentration of 2×106 cells/mL, and the effects of varying concentrations of dimethylsulfoxide(DMSO,10,15or20%)were assessed after freezing at -70℃ and then liquid nitrogen After 12 months of frozen storage, these cells were thawed rapidly at 37℃ and trypan blue exclusion staining and attachment to culture dishes were assessed as measures of viability. The viabilities for PLC,ILC, and ALC were over85% in the presence of 15% DMSO. Increasing the concentration of fetal calf serum (FCS)in the DMSO-based medium to 20% had no effect on survival after freezing and thawing. In consideration of possible effects of FCS components on steroidogenic function, a serum-free cryopreservative medium was adopted. S-DMEM/F12+15%DMSO. After 12 months in this medium at liquid nitrogen, the Leydig cell steroidogenic capacity in response to maximal challenge doses of luteinizing hormone(LH, 100ng/mL) was unchanged compared to freshly isolated control cells (e.g.,ILC freshly isolated 27.36±4.74 vs. frozen 30.14±1.43ng/106cell ·3hr). Furthermore, the steady state messenger RNA levels for Leydig cell specific transcripts including LH receptor, steroidoenic acute regulatory protein(StAR), cytochrome P450 side chain cleavage enzyme, 17α-hydroxylase/20-lysase,3β-hydroxysteroid dehydrogenase 1 and 2 and 17β-hydroxysteroid dehydrogenase 3, were maintained. This study demonstrated that purified rat progenitor, immature and adult Leydig cells can be frozen and that the cryopreserved cells retai

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中国男科学杂志 2001年第4期15卷 247-250页

作者：高惠宝 ,胡燕琴 ,童明汉 ,matthew P.hardy 上海第二医科大学生殖生物学实验室上海第二医科大学生殖生物学实验室上海第二医科大学生殖生物学实验室人口委员会生物医学研究中心上海200025 上海200025 上海200025 美国

已往的研究发现 ,大鼠Leydig细胞中的 11β 羟类固醇脱氢酶 (11β HSD)通过控制细胞内皮质酮 (大鼠体内的糖皮质激素 )浓度调节睾酮合成。本研究通过观察 11β HSD活性可调的大鼠动物模型中Leydig细胞内 11β HSDmRNA的表达情况 ,以明... 详细信息

已往的研究发现 ,大鼠Leydig细胞中的 11β 羟类固醇脱氢酶 (11β HSD)通过控制细胞内皮质酮 (大鼠体内的糖皮质激素 )浓度调节睾酮合成。本研究通过观察 11β HSD活性可调的大鼠动物模型中Leydig细胞内 11β HSDmRNA的表达情况 ,以明确这些表达是否和酶活性测定结果具有一致性。结果表明 ,大鼠Leydig细胞中的11β HSDmRNA的表达量和其酶活性水平具有明显的一致性。在大鼠体内 ,生理水平或高浓度的皮质酮调节Leydig细胞中 11β HSD活性是通过调节细胞中稳定性mRNA的表达实现的。

关键词： Leydig细胞 11 β-羟类固醇脱氢酶糖皮质激素 mRNA表达

皮质酮诱导青春期大鼠睾丸间质细胞凋亡的研究

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中国男科学杂志 2000年第3期14卷 170-172页

作者：高惠宝童明汉胡燕琴 )matthewP.hardy 上海第二医科大学生殖生物学实验室上海200025 人口委员会生物医学研究中心(美国

本研究目的旨在观察皮质酮能否诱导青春期大鼠睾丸间质细胞凋亡。用皮质酮分别经体内、外途径处理大鼠睾丸间质细胞。凋亡细胞经碘化丙碇 (PI)标记后用流式细胞仪检测。体外研究结果表明 ,经 1 0 0nM皮质酮处理 2 4小时后的睾丸间质细... 详细信息

本研究目的旨在观察皮质酮能否诱导青春期大鼠睾丸间质细胞凋亡。用皮质酮分别经体内、外途径处理大鼠睾丸间质细胞。凋亡细胞经碘化丙碇 (PI)标记后用流式细胞仪检测。体外研究结果表明 ,经 1 0 0nM皮质酮处理 2 4小时后的睾丸间质细胞 ,其凋亡量 (36 .5 % )显著高于对照组 (1 2 .7%。P <0 .0 1 )。在体研究得到类似结果 ,经皮质酮 (2 .5mg/ 1 0 0 g体重 )处理 2 4小时后的大鼠 ,其纯化的睾丸间质细胞凋亡量 (2 0 .5 % )显著高于对照组(5 .0 % ,P <0 .0 1 )。上述结果提示 :皮质酮在体内、外均能诱导青春期大鼠睾丸间质细胞凋亡。这一现象可能是高糖皮质激素血症导致间质细胞中睾酮合成量减少的原因之一。

关键词：皮质酮睾丸间质细胞细胞凋亡青春期

Guest editorial:Molybdenum alloying:more than hardenability

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Advances in Manufacturing 2020年第1期8卷 1-2页

作者： hardy Mohrbacher NiobelCon bvba SchildeBelgium Department of Materials Engineering KU LeuvenLeuvenBelgium

Molybdenum is a transitional metal in the periodic table of elements where it ranks in position 42 in the 5th period and group VI *** a high melting point of 2623℃,molybdenum belongs to the so-called refractory ***,as pure metal it finds many applications where high temperatures are encountered during operation,for example in ***,nearly 80%of all molybdenum produced every year by the world’s mining industry is used as addition to iron and steel *** and alloy steels account for 40%of molybdenum use,followed by stainless steels(23%),tool steels and castings(both around 8%).

关键词： alloying alloy steel

Metallurgical concepts for optimized processing and properties of carburizing steel

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Advances in Manufacturing 2016年第2期4卷 105-114页

作者： hardy Mohrbacher NiobelCon bvba Schilde Belgium

Carburized steel grades are widely used in applications where high surface near hardness is required in combination with good core toughness as well as high strength and fatigue resistance. The process of carburizing lower to medium carbon containing steel can generally provide this combination of properties and has been prac- ticed for several decades. Such steel is essential in the vehicle power-train, machines and power generation equipment. However, the increasing performance demands by such applications as well as economical considerations forced steel producers to develop better alloys and fabri- cators to design more efficient manufacturing processes. The present paper describes recent concepts for alloy design optimization of carburizing steel and demonstrates the forthcoming beneficial consequences with regard to manufacturing processes and final properties.

关键词： High temperature carburizing Grain sizecontrol Distortion control - Integrated manufacturing Plasma nitriding - Micro pitting - Tooth root fatiguestrength Molybdenum steel Niobium microalloying

Guest editorial of "Application of high strength steels in lightweight commercial vehicles"

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Advances in Manufacturing 2015年第1期3卷 1-2页

作者： hardy Mohrbacher NiobelCon bvba SchildeBelgium

New and increasingly sharp laws for the reduction of emissions from commercial vehicles entered into force in the European Union since 1993 with the aim of substan-tially reducing pollutants and emissions from trucks and buses. Thereby the maximum levels for the emission of particulate matter （basically soot particles） as well as oxides of nitrogen （NOx） have been subsequently lowered. To comply with these demands, commercial vehicle producers had to introduce new emission reducing technologies of which exhaust-gas recirculation （EGR）,

关键词： Guest editorial of Application of high strength steels in lightweight commercial vehicles high